Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Cancer Stem Cells and Chemoresistance in Ewing Sarcoma

Author(s): Rafael Pereira dos Santos, Rafael Roesler*, Lauro Gregianin, André T. Brunetto, Mariane da Cunha Jaeger, Algemir Lunardi Brunetto and Caroline Brunetto de Farias

Volume 18, Issue 7, 2023

Published on: 27 August, 2022

Page: [926 - 936] Pages: 11

DOI: 10.2174/1574888X17666220627114710

Price: $65

Abstract

Resistance to chemotherapy poses a major challenge for cancer treatment. Reactivating a stem cell program resembling that seen in embryonic development can lead cancer cells to acquire a stem-cell phenotype characterized by expression of stemness genes, pluripotency, high self-renewal ability, and tumor-initiating capability. These cancer stem cells (CSCs) are usually resistant to anticancer drugs and are likely involved in treatment failure in many cancer types. Ewing sarcoma (ES) is a pediatric cancer type typically resulting from a typical genetic alteration affecting bone or soft tissues. Despite advances in treatment, survival prognostic remains poor for patients with refractory or recurrent disease. Here, we review the increasing evidence indicating that ES tumors contain a CSC subpopulation expressing stem cell genes, including BM1, OCT3/4, NANOG, and SOX2, that plays a role in resistance to drug treatment, and current experimental strategies that successfully counteract chemoresistance mediated by CSCs in ES.

Keywords: Ewing sarcoma, sarcoma, pediatric cancer, chemoresistance, cancer stem cell, stem cell.

« Previous Next »
[1]
Lawlor ER, Thiele CJ. Epigenetic changes in pediatric solid tumors: Promising new targets. Clin Cancer Res 2012; 18(10): 2768-79.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-1921] [PMID: 22589485]
[2]
Marshall GM, Carter DR, Cheung BB, et al. The prenatal origins of cancer. Nat Rev Cancer 2014; 14(4): 277-89.
[http://dx.doi.org/10.1038/nrc3679] [PMID: 24599217]
[3]
Chaturvedi A, Hoffman LM, Welm AL, Lessnick SL, Beckerle MC. The EWS/FLI oncogene drives changes in cellular morphology, adhesion, and migration in Ewing sarcoma. Genes Cancer 2012; 3(2): 102-16.
[http://dx.doi.org/10.1177/1947601912457024] [PMID: 23050043]
[4]
Riggi N, Knoechel B, Gillespie SM, et al. EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell 2014; 26(5): 668-81.
[http://dx.doi.org/10.1016/j.ccell.2014.10.004] [PMID: 25453903]
[5]
Eaton BR, Claude L, Indelicato DJ, et al. Ewing sarcoma. Pediatr Blood Cancer 2021; 68(S2) (Suppl. 2): e28355.
[http://dx.doi.org/10.1002/pbc.28355] [PMID: 33818887]
[6]
Grünewald TGP, Cidre-Aranaz F, Surdez D, et al. Ewing sarcoma. Nat Rev Dis Primers 2018; 4(1): 5.
[http://dx.doi.org/10.1038/s41572-018-0003-x] [PMID: 29977059]
[7]
Riggi N, Suvà ML, Stamenkovic I. Ewing’s Sarcoma. N Engl J Med 2021; 384(2): 154-64.
[http://dx.doi.org/10.1056/NEJMra2028910] [PMID: 33497548]
[8]
Riggi N, Cironi L, Provero P, et al. Development of Ewing’s sarcoma from primary bone marrow-derived mesenchymal progenitor cells. Cancer Res 2005; 65(24): 11459-68.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1696] [PMID: 16357154]
[9]
Riggi N, Suvà ML, Suvà D, et al. EWS-FLI-1 expression triggers a Ewing’s sarcoma initiation program in primary human mesenchymal stem cells. Cancer Res 2008; 68(7): 2176-85.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1761] [PMID: 18381423]
[10]
Sole A, Grossetête S, Heintzé M, et al. Unraveling Ewing sarcoma tumorigenesis originating from patient-derived mesenchymal stem cells. Cancer Res 2021; 81(19): 4994-5006.
[http://dx.doi.org/10.1158/0008-5472.CAN-20-3837] [PMID: 34341072]
[11]
El Beaino M, Liu J, Wasylishen AR, et al. Loss of Stag2 cooperates with EWS-FLI1 to transform murine Mesenchymal stem cells. BMC Cancer 2020; 20(1): 3.
[http://dx.doi.org/10.1186/s12885-019-6465-8] [PMID: 31898537]
[12]
Fadul J, Bell R, Hoffman LM, Beckerle MC, Engel ME, Lessnick SL. EWS/FLI utilizes NKX2-2 to repress mesenchymal features of Ewing sarcoma. Genes Cancer 2015; 6(3-4): 129-43.
[http://dx.doi.org/10.18632/genesandcancer.57] [PMID: 26000096]
[13]
Collini P, Mezzelani A, Modena P, et al. Evidence of neural differentiation in a case of post-therapy primitive neuroectodermal tumor/Ewing sarcoma of bone. Am J Surg Pathol 2003; 27(8): 1161-6.
[http://dx.doi.org/10.1097/00000478-200308000-00016] [PMID: 12883251]
[14]
Franchi A, Pasquinelli G, Cenacchi G, et al. Immunohistochemical and ultrastructural investigation of neural differentiation in Ewing sarcoma/PNET of bone and soft tissues. Ultrastruct Pathol 2001; 25(3): 219-25.
[http://dx.doi.org/10.1080/01913120120194] [PMID: 11465478]
[15]
Weissferdt A, Kalhor N, Moran CA. Ewing sarcoma with extensive neural differentiation: A clinicopathologic, immunohistochemical, and molecular analysis of three cases. Am J Clin Pathol 2015; 143(5): 659-64.
[http://dx.doi.org/10.1309/AJCPFHFX07JFCRGU] [PMID: 25873499]
[16]
Staege MS, Hutter C, Neumann I, et al. DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets. Cancer Res 2004; 64(22): 8213-21.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-4059] [PMID: 15548687]
[17]
Cavazzana AO, Miser JS, Jefferson J, Triche TJ. Experimental evidence for a neural origin of Ewing’s sarcoma of bone. Am J Pathol 1987; 127(3): 507-18.
[PMID: 3035930]
[18]
Lizard-Nacol S, Lizard G, Justrabo E, Turc-Carel C. Immunologic characterization of Ewing’s sarcoma using mesenchymal and neural markers. Am J Pathol 1989; 135(5): 847-55.
[PMID: 2479272]
[19]
Rorie CJ, Thomas VD, Chen P, Pierce HH, O’Bryan JP, Weissman BE. The Ews/Fli-1 fusion gene switches the differentiation program of neuroblastomas to Ewing sarcoma/peripheral primitive neuroectodermal tumors. Cancer Res 2004; 64(4): 1266-77.
[http://dx.doi.org/10.1158/0008-5472.CAN-03-3274] [PMID: 14973077]
[20]
Baliko F, Bright T, Poon R, Cohen B, Egan SE, Alman BA. Inhibition of notch signaling induces neural differentiation in Ewing sarcoma. Am J Pathol 2007; 170(5): 1686-94.
[http://dx.doi.org/10.2353/ajpath.2007.060971] [PMID: 17456774]
[21]
Rocchi A, Manara MC, Sciandra M, et al. CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis. J Clin Invest 2010; 120(3): 668-80.
[http://dx.doi.org/10.1172/JCI36667] [PMID: 20197622]
[22]
Ventura S, Aryee DN, Felicetti F, et al. CD99 regulates neural differentiation of Ewing sarcoma cells through miR-34a-Notch-mediated control of NF-κB signaling. Oncogene 2016; 35(30): 3944-54.
[http://dx.doi.org/10.1038/onc.2015.463] [PMID: 26616853]
[23]
De Feo A, Sciandra M, Ferracin M, et al. Exosomes from CD99-deprived Ewing sarcoma cells reverse tumor malignancy by inhibiting cell migration and promoting neural differentiation. Cell Death Dis 2019; 10(7): 471.
[http://dx.doi.org/10.1038/s41419-019-1675-1] [PMID: 31209202]
[24]
von Levetzow C, Jiang X, Gwye Y, et al. Modeling initiation of Ewing sarcoma in human neural crest cells. PLoS One 2011; 6(4): e19305.
[http://dx.doi.org/10.1371/journal.pone.0019305] [PMID: 21559395]
[25]
García-García L, Fernández-Tabanera E, Cervera ST, et al. The transcription factor FEZF1, a direct target of EWSR1-FLI1 in Ewing sarcoma cells, regulates the expression of neural-specific genes. Cancers (Basel) 2021; 13(22): 5668.
[http://dx.doi.org/10.3390/cancers13225668] [PMID: 34830820]
[26]
Scannell CA, Pedersen EA, Mosher JT, et al. LGR5 is expressed by Ewing sarcoma and potentiates Wnt/β-catenin signaling. Front Oncol 2013; 3: 81.
[http://dx.doi.org/10.3389/fonc.2013.00081] [PMID: 23596566]
[27]
Zhou Z, Yu L, Kleinerman ES. EWS-FLI-1 regulates the neuronal repressor gene REST, which controls Ewing sarcoma growth and vascular morphology. Cancer 2014; 120(4): 579-88.
[http://dx.doi.org/10.1002/cncr.28555] [PMID: 24415532]
[28]
Souza BK, da Costa Lopez PL, Menegotto PR, et al. Targeting histone deacetylase activity to arrest cell growth and promote neural differentiation in Ewing sarcoma. Mol Neurobiol 2018; 55(9): 7242-58.
[http://dx.doi.org/10.1007/s12035-018-0874-6] [PMID: 29397557]
[29]
Clevers H. The cancer stem cell: Premises, promises and challenges. Nat Med 2011; 17(3): 313-9.
[http://dx.doi.org/10.1038/nm.2304] [PMID: 21386835]
[30]
Ebben JD, Treisman DM, Zorniak M, Kutty RG, Clark PA, Kuo JS. The cancer stem cell paradigm: A new understanding of tumor development and treatment. Expert Opin Ther Targets 2010; 14(6): 621-32.
[http://dx.doi.org/10.1517/14712598.2010.485186] [PMID: 20426697]
[31]
Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell 2014; 14(3): 275-91.
[http://dx.doi.org/10.1016/j.stem.2014.02.006] [PMID: 24607403]
[32]
Meacham CE, Morrison SJ. Tumour heterogeneity and cancer cell plasticity. Nature 2013; 501(7467): 328-37.
[http://dx.doi.org/10.1038/nature12624] [PMID: 24048065]
[33]
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997; 3(7): 730-7.
[http://dx.doi.org/10.1038/nm0797-730] [PMID: 9212098]
[34]
Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 2004; 5(7): 738-43.
[http://dx.doi.org/10.1038/ni1080] [PMID: 15170211]
[35]
Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994; 367(6464): 645-8.
[http://dx.doi.org/10.1038/367645a0] [PMID: 7509044]
[36]
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100(7): 3983-8.
[http://dx.doi.org/10.1073/pnas.0530291100] [PMID: 12629218]
[37]
Bomken S, Fiser K, Heidenreich O, Vormoor J. Understanding the cancer stem cell. Br J Cancer 2010; 103(4): 439-45.
[http://dx.doi.org/10.1038/sj.bjc.6605821] [PMID: 20664590]
[38]
Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature 2007; 445(7123): 111-5.
[http://dx.doi.org/10.1038/nature05384] [PMID: 17122771]
[39]
Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003; 63(18): 5821-8.
[PMID: 14522905]
[40]
Komuro H, Saihara R, Shinya M, et al. Identification of side population cells (stem-like cell population) in pediatric solid tumor cell lines. J Pediatr Surg 2007; 42(12): 2040-5.
[http://dx.doi.org/10.1016/j.jpedsurg.2007.08.026] [PMID: 18082704]
[41]
Suvà ML, Riggi N, Stehle JC, et al. Identification of cancer stem cells in Ewing’s sarcoma. Cancer Res 2009; 69(5): 1776-81.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-2242] [PMID: 19208848]
[42]
Hotfilder M, Mallela N, Seggewiß J, Dirksen U, Korsching E. Defining a characteristic gene expression set responsible for cancer stem cell-like features in a sub-population of Ewing sarcoma cells CADO-ES1. Int J Mol Sci 2018; 19(12): 3908.
[http://dx.doi.org/10.3390/ijms19123908] [PMID: 30563222]
[43]
Riggi N, Suvà ML, De Vito C, et al. EWS-FLI-1 modulates miRNA145 and SOX2 expression to initiate mesenchymal stem cell reprogramming toward ewing sarcoma cancer stem cells. Genes Dev 2010; 24(9): 916-32.
[http://dx.doi.org/10.1101/gad.1899710] [PMID: 20382729]
[44]
De Vito C, Riggi N, Cornaz S, et al. A TARBP2-dependent miRNA expression profile underlies cancer stem cell properties and provides candidate therapeutic reagents in Ewing sarcoma. Cancer Cell 2012; 21(6): 807-21.
[http://dx.doi.org/10.1016/j.ccr.2012.04.023] [PMID: 22698405]
[45]
Guzel Tanoglu E, Ozturk S. miR-145 suppresses epithelial-mesenchymal transition by targeting stem cells in Ewing sarcoma cells. Bratisl Lek Listy 2021; 122(1): 71-7.
[http://dx.doi.org/10.4149/BLL_2021_009] [PMID: 33393324]
[46]
Cornaz-Buros S, Riggi N, DeVito C, et al. Targeting cancer stem-like cells as an approach to defeating cellular heterogeneity in Ewing sarcoma. Cancer Res 2014; 74(22): 6610-22.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-1106] [PMID: 25261238]
[47]
Heinen TE, Dos Santos RP, da Rocha A, et al. Trk inhibition reduces cell proliferation and potentiates the effects of chemotherapeutic agents in ewing sarcoma. Oncotarget 2016; 7(23): 34860-80.
[http://dx.doi.org/10.18632/oncotarget.8992] [PMID: 27145455]
[48]
Donnenberg VS, Donnenberg AD. Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis. J Clin Pharmacol 2005; 45(8): 872-7.
[http://dx.doi.org/10.1177/0091270005276905] [PMID: 16027397]
[49]
Najafi M, Mortezaee K, Majidpoor J. Cancer stem cell (CSC) resistance drivers. Life Sci 2019; 234: 116781.
[http://dx.doi.org/10.1016/j.lfs.2019.116781] [PMID: 31430455]
[50]
Doherty MR, Smigiel JM, Junk DJ, Jackson MW. Cancer stem cell plasticity drives therapeutic resistance. Cancers (Basel) 2016; 8(1): 8.
[http://dx.doi.org/10.3390/cancers8010008] [PMID: 26742077]
[51]
Cabrera MC, Hollingsworth RE, Hurt EM. Cancer stem cell plasticity and tumor hierarchy. World J Stem Cells 2015; 7(1): 27-36.
[http://dx.doi.org/10.4252/wjsc.v7.i1.27] [PMID: 25621103]
[52]
Das PK, Pillai S, Rakib MA, et al. Plasticity of cancer stem cell: Origin and role in disease progression and therapy resistance. Stem Cell Rev Rep 2020; 16(2): 397-412.
[http://dx.doi.org/10.1007/s12015-019-09942-y] [PMID: 31965409]
[53]
Awad O, Yustein JT, Shah P, et al. High ALDH activity identifies chemotherapy-resistant Ewing’s sarcoma stem cells that retain sensitivity to EWS-FLI1 inhibition. PLoS One 2010; 5(11): e13943.
[http://dx.doi.org/10.1371/journal.pone.0013943] [PMID: 21085683]
[54]
Fujii H, Honoki K, Tsujiuchi T, Kido A, Yoshitani K, Takakura Y. Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines. Int J Oncol 2009; 34(5): 1381-6.
[http://dx.doi.org/10.3892/ijo_00000265] [PMID: 19360350]
[55]
Yang M, Zhang R, Yan M, Ye Z, Liang W, Luo Z. Detection and characterization of side population in Ewing’s sarcoma SK-ES-1 cells in vitro. Biochem Biophys Res Commun 2010; 391(1): 1062-6.
[http://dx.doi.org/10.1016/j.bbrc.2009.12.020] [PMID: 20004177]
[56]
Jiang X, Gwye Y, Russell D, et al. CD133 expression in chemo-resistant Ewing sarcoma cells. BMC Cancer 2010; 10(1): 116.
[http://dx.doi.org/10.1186/1471-2407-10-116] [PMID: 20346143]
[57]
Moore JB IV, Loeb DM, Hong KU, et al. Epigenetic reprogramming and re-differentiation of a Ewing sarcoma cell line. Front Cell Dev Biol 2015; 3: 15.
[http://dx.doi.org/10.3389/fcell.2015.00015] [PMID: 25806369]
[58]
Honoki K. Do stem-like cells play a role in drug resistance of sarcomas? Expert Rev Anticancer Ther 2010; 10(2): 261-70.
[http://dx.doi.org/10.1586/era.09.184] [PMID: 20132001]
[59]
Dasgupta A, Trucco M, Rainusso N, et al. Metabolic modulation of Ewing sarcoma cells inhibits tumor growth and stem cell properties. Oncotarget 2017; 8(44): 77292-308.
[http://dx.doi.org/10.18632/oncotarget.20467] [PMID: 29100387]
[60]
Wilky BA, Kim C, McCarty G, et al. RNA helicase DDX3: A novel therapeutic target in Ewing sarcoma. Oncogene 2016; 35(20): 2574-83.
[http://dx.doi.org/10.1038/onc.2015.336] [PMID: 26364611]
[61]
Attia S, Bolejack V, Ganjoo KN, et al. A phase II trial of regorafenib (REGO) in patients (pts) with advanced Ewing sarcoma and related tumors (EWS) of soft tissue and bone: SARC024 trial results. J Clin Oncol 2017; 35(15) (Suppl.): 11005.
[http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.11005]
[62]
Choy E, Butrynski JE, Harmon DC, et al. Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy. BMC Cancer 2014; 14(1): 813.
[http://dx.doi.org/10.1186/1471-2407-14-813] [PMID: 25374341]
[63]
Fleuren ED, Roeffen MH, Leenders WP, et al. Expression and clinical relevance of MET and ALK in Ewing sarcomas. Int J Cancer 2013; 133(2): 427-36.
[http://dx.doi.org/10.1002/ijc.28047] [PMID: 23335077]
[64]
Italiano A, Mir O, Mathoulin-Pelissier S, et al. Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial. Lancet Oncol 2020; 21(3): 446-55.
[http://dx.doi.org/10.1016/S1470-2045(19)30825-3] [PMID: 32078813]
[65]
Malempati S, Weigel B, Ingle AM, et al. Phase I/II trial and pharmacokinetic study of cixutumumab in pediatric patients with refractory solid tumors and ewing sarcoma: A report from the children’s oncology group. J Clin Oncol 2012; 30(3): 256-62.
[http://dx.doi.org/10.1200/JCO.2011.37.4355] [PMID: 22184397]
[66]
Naing A, LoRusso P, Fu S, et al. Insulin growth factor-receptor (IGF-1R) antibody cixutumumab combined with the mTOR inhibitor temsirolimus in patients with refractory Ewing’s sarcoma family tumors. Clin Cancer Res 2012; 18(9): 2625-31.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-0061] [PMID: 22465830]
[67]
Wagner LM, Fouladi M, Ahmed A, et al. Phase II study of cixutumumab in combination with temsirolimus in pediatric patients and young adults with recurrent or refractory sarcoma: A report from the Children’s Oncology Group. Pediatr Blood Cancer 2015; 62(3): 440-4.
[http://dx.doi.org/10.1002/pbc.25334] [PMID: 25446280]
[68]
Tirode F, Surdez D, Ma X, et al. Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov 2014; 4(11): 1342-53.
[http://dx.doi.org/10.1158/2159-8290.CD-14-0622] [PMID: 25223734]
[69]
Brunetto AL, Castillo LA, Petrilli AS, et al. Carboplatin in the treatment of Ewing sarcoma: Results of the first Brazilian collaborative study group for ewing sarcoma family tumors-EWING1. Pediatr Blood Cancer 2015; 62(10): 1747-53.
[http://dx.doi.org/10.1002/pbc.25562] [PMID: 25917418]
[70]
Gaspar N, Hawkins DS, Dirksen U, et al. Ewing sarcoma: current management and future approaches through collaboration. J Clin Oncol 2015; 33(27): 3036-46.
[http://dx.doi.org/10.1200/JCO.2014.59.5256] [PMID: 26304893]
[71]
Grier HE, Krailo MD, Tarbell NJ, et al. Addition of ifosfamide and etoposide to standard chemotherapy for Ewing’s sarcoma and primitive neuroectodermal tumor of bone. N Engl J Med 2003; 348(8): 694-701.
[http://dx.doi.org/10.1056/NEJMoa020890] [PMID: 12594313]
[72]
Esiashvili N, Goodman M, Marcus RB Jr. Changes in incidence and survival of ewing sarcoma patients over the past 3 decades: Surveillance Epidemiology and End Results data. J Pediatr Hematol Oncol 2008; 30(6): 425-30.
[http://dx.doi.org/10.1097/MPH.0b013e31816e22f3] [PMID: 18525458]
[73]
Chen Y, Hesla AC, Lin Y, et al. Transcriptome profiling of Ewing sarcomas - treatment resistance pathways and IGF-dependency. Mol Oncol 2020; 14(5): 1101-17.
[http://dx.doi.org/10.1002/1878-0261.12655] [PMID: 32115849]
[74]
Horbach L, Sinigaglia M, Da Silva CA, et al. Gene expression changes associated with chemotherapy resistance in Ewing sarcoma cells. Mol Clin Oncol 2018; 8(6): 719-24.
[http://dx.doi.org/10.3892/mco.2018.1608] [PMID: 29844902]
[75]
Iida K, Fukushi J, Matsumoto Y, et al. miR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor. Cancer Cell Int 2013; 13(1): 21.
[http://dx.doi.org/10.1186/1475-2867-13-21] [PMID: 23497288]
[76]
Ribeiro-Dantas MDC, Oliveira Imparato D, Dalmolin MGS, et al. Reverse engineering of Ewing sarcoma regulatory network uncovers PAX7 and RUNX3 as master regulators associated with good prognosis. Cancers (Basel) 2021; 13(8): 1860.
[http://dx.doi.org/10.3390/cancers13081860] [PMID: 33924679]
[77]
Santoro M, Menegaz BA, Lamhamedi-Cherradi SE, et al. Modeling stroma-induced drug resistance in a tissue-engineered tumor model of Ewing sarcoma. Tissue Eng Part A 2017; 23(1-2): 80-9.
[http://dx.doi.org/10.1089/ten.tea.2016.0369] [PMID: 27923328]
[78]
Serra M, Hattinger CM, Pasello M, et al. Impact of ABC transporters in osteosarcoma and Ewing’s sarcoma: Which are involved in chemoresistance and which are not? Cells 2021; 10(9): 2461.
[http://dx.doi.org/10.3390/cells10092461] [PMID: 34572110]
[79]
Erkizan HV, Kong Y, Merchant M, et al. A small molecule blocking oncogenic protein EWS-FLI1 interaction with RNA helicase A inhibits growth of ewing’s sarcoma. Nat Med 2009; 15(7): 750-6.
[http://dx.doi.org/10.1038/nm.1983] [PMID: 19584866]
[80]
Pishas KI, Lessnick SL. Recent advances in targeted therapy for Ewing sarcoma. F1000 Res 2016; 5.
[http://dx.doi.org/10.12688/f1000research.8631.1]
[81]
Subbiah V, Anderson P. Targeted therapy of ewing’s sarcoma. Sarcoma 2011; 2011: 686985.
[http://dx.doi.org/10.1155/2011/686985] [PMID: 21052545]
[82]
Amin HM, Morani AC, Daw NC, et al. IGF-1R/mTOR targeted therapy for Ewing sarcoma: a meta-analysis of five IGF-1R-related trials matched to proteomic and radiologic predictive biomarkers. Cancers (Basel) 2020; 12(7): 1768.
[http://dx.doi.org/10.3390/cancers12071768] [PMID: 32630797]
[83]
Jin W. The role of tyrosine kinases as a critical prognostic parameter and its targeted therapies in Ewing sarcoma. Front Cell Dev Biol 2020; 8: 613.
[http://dx.doi.org/10.3389/fcell.2020.00613] [PMID: 32754598]
[84]
Kersting N, Kunzler Souza B, Araujo Vieira I, et al. Epidermal growth factor receptor regulation of Ewing sarcoma cell function. Oncology 2018; 94(6): 383-93.
[http://dx.doi.org/10.1159/000487143] [PMID: 29539615]
[85]
Kurzrock R, Patnaik A, Aisner J, et al. A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors. Clin Cancer Res 2010; 16(8): 2458-65.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-3220] [PMID: 20371689]
[86]
Lamhamedi-Cherradi SE, Menegaz BA, Ramamoorthy V, et al. IGF-1R and mTOR blockade: Novel resistance mechanisms and synergistic drug combinations for Ewing sarcoma. J Natl Cancer Inst 2016; 108(12): djw182.
[http://dx.doi.org/10.1093/jnci/djw182] [PMID: 27576731]
[87]
Olmos D, Postel-Vinay S, Molife LR, et al. Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing’s sarcoma: a phase 1 expansion cohort study. Lancet Oncol 2010; 11(2): 129-35.
[http://dx.doi.org/10.1016/S1470-2045(09)70354-7] [PMID: 20036194]
[88]
Ma Y, Baltezor M, Rajewski L, et al. Targeted inhibition of histone deacetylase leads to suppression of Ewing sarcoma tumor growth through an unappreciated EWS-FLI1/HDAC3/HSP90 signaling axis. J Mol Med (Berl) 2019; 97(7): 957-72.
[http://dx.doi.org/10.1007/s00109-019-01782-0] [PMID: 31025088]
[89]
Nacev BA, Jones KB, Intlekofer AM, et al. The epigenomics of sarcoma. Nat Rev Cancer 2020; 20(10): 608-23.
[http://dx.doi.org/10.1038/s41568-020-0288-4] [PMID: 32782366]
[90]
Sheffield NC, Pierron G, Klughammer J, et al. DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma. Nat Med 2017; 23(3): 386-95.
[http://dx.doi.org/10.1038/nm.4273] [PMID: 28134926]
[91]
Dalal S, Berry AM, Cullinane CJ, et al. Vascular endothelial growth factor: A therapeutic target for tumors of the Ewing’s sarcoma family. Clin Cancer Res 2005; 11(6): 2364-78.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-1201] [PMID: 15788688]
[92]
Hatina J, Kripnerova M, Houfkova K, et al. Sarcoma stem cell heterogeneity. Adv Exp Med Biol 2019; 1123: 95-118.
[http://dx.doi.org/10.1007/978-3-030-11096-3_7] [PMID: 31016597]
[93]
Leuchte K, Altvater B, Hoffschlag S, et al. Anchorage-independent growth of Ewing sarcoma cells under serum-free conditions is not associated with stem-cell like phenotype and function. Oncol Rep 2014; 32(2): 845-52.
[http://dx.doi.org/10.3892/or.2014.3269] [PMID: 24927333]
[94]
Frank NY, Schatton T, Frank MH. The therapeutic promise of the cancer stem cell concept. J Clin Invest 2010; 120(1): 41-50.
[http://dx.doi.org/10.1172/JCI41004] [PMID: 20051635]
[95]
Tang C, Ang BT, Pervaiz S. Cancer stem cell: Target for anti-cancer therapy. FASEB J 2007; 21(14): 3777-85.
[http://dx.doi.org/10.1096/fj.07-8560rev] [PMID: 17625071]
[96]
Todorova R. Ewing’s sarcoma cancer stem cell targeted therapy. Curr Stem Cell Res Ther 2014; 9(1): 46-62.
[http://dx.doi.org/10.2174/1574888X08666131203123125] [PMID: 24294922]
[97]
Aynaud MM, Mirabeau O, Gruel N, et al. Transcriptional programs define intratumoral heterogeneity of Ewing sarcoma at single-cell resolution. Cell Rep 2020; 30(6): 1767-1779.e6.
[http://dx.doi.org/10.1016/j.celrep.2020.01.049] [PMID: 32049009]
[98]
Salguero-Aranda C, Amaral AT, Olmedo-Pelayo J, Diaz-Martin J, Álava E. Breakthrough technologies reshape the Ewing sarcoma molecular landscape. Cells 2020; 9(4): 804.
[http://dx.doi.org/10.3390/cells9040804] [PMID: 32225029]

Rights & Permissions Print Cite
Article Metrics
4
© 2024 Bentham Science Publishers | Privacy Policy